Dopamine Neuron Activity and Stress Signaling as Links Between Social Hierarchy and Psychopathology Vulnerability.

BACKGROUND: Social status in humans, generally reflected by socioeconomic status, has been associated, when constrained, with heightened vulnerability to pathologies including psychiatric diseases. Social hierarchy in mice translates into individual and interdependent behavioral strategies of animals within a group. The rules leading to the emergence of a social organization are elusive, and detangling the contribution of social status from other factors, whether environmental or genetic, to normal and pathological behaviors remains challenging. METHODS: We investigated the mechanisms shaping the emergence of a social hierarchy in isogenic C57BL/6 mice raised in groups of 4 using conditional mutant mouse models and chemogenetic manipulation of dopamine midbrain neuronal activity. We further studied the evolution of behavioral traits and the vulnerability to psychopathological-like phenotypes according to the social status of the animals. RESULTS: Higher sociability predetermined higher social hierarchy in the colony. Upon hierarchy establishment, higher-ranked mice showed increased anxiety and better cognitive abilities in a working memory task. Strikingly, the higher-ranked mice displayed a reduced activity of dopaminergic neurons within the ventral tegmental area, paired with a decreased behavioral response to cocaine and a decreased vulnerability to depressive-like behaviors following repeated social defeats. The pharmacogenetic inhibition of this neuronal population and the genetic inactivation of glucocorticoid receptor signaling in dopamine-sensing brain areas that resulted in decreased dopaminergic activity promoted accession to higher social ranks. CONCLUSIONS: Dopamine activity and its modulation by the stress response shapes social organization in mice, potentially linking interindividual and social status differences in vulnerability to psychopathologies.

Using information technology to integrate tobacco use treatment in routine oncology care: Lessons learned from the U.S. Cancer Center Cessation Initiative Cancer Centers.

Background: Cancer patients who receive evidence-based tobacco-dependence treatment are more likely to quit and remain abstinent, but tobacco treatment programs (TTPs) are not consistently offered. In 2017, the U.S. National Cancer Institute, through the Cancer Moonshot, funded the Cancer Center Cessation Initiative (C3I). C3I supports 52 cancer centers to implement and expand evidence-based tobacco treatment in routine oncology care. Integration into routine care involves the use of health information technology (IT), including modifying electronic health records and clinical workflows. Here, we examine C3I cancer centers' IT leadership involvement and experiences in tobacco-dependence treatment implementation. Method: This qualitative study of C3I-funded cancer centers integrated data from online surveys and in-person, semistructured interviews with IT leaders. We calculated descriptive statistics of survey data and applied content analysis to interview transcripts. Results: Themes regarding IT personnel included suggestions to involve IT early, communicate regularly, understand the roles and influence of the IT team, and match program design with IT funding and resources. Themes regarding electronic health record (EHR) modifications included beginning modifications early to account for long lead time to make changes, working with IT to identify and adapt existing EHR tools for TTP or designing tools that will support a desired workflow developed with end-users, and working with IT personnel to make sure TTPs comply with system and state policies (e.g., privacy laws). Conclusions: The experiences of C3I cancer centers regarding the use of health IT to enhance tobacco-dependence treatment program implementation can guide cancer centers and community oncology practices to potentially enhance TTP implementation and patient outcomes.

Almost a quarter of patients first diagnosed with cancer report current cigarette smoking. There are tobacco treatment programs (TTPs) that effectively help patients quit smoking to improve cancer treatment response, survival, and quality-of-life. In 2017, the U.S. National Cancer Institute (NCI) funded the Cancer Center Cessation Initiative (C3I) and supported 52 cancer centers to implement these TTPs. A key component of these programs is the information technology (IT) necessary to refer patients to the program and document their progress. As coordinators of C3I, our team conducted interviews with IT leaders at these cancer centers to learn about the implementation of the programs. IT leaders suggested that IT teams be involved early in the program implementation process and that leaders communicate with the IT team regularly to address necessary changes to referral and documentation systems. IT teams are important to involve early and regularly throughout the TTP implementation process because they have unique knowledge of how funding, policy, and existing technological tools will impact the implementation and success of the program. Our findings emphasize the importance of involving IT teams early in the planning process for such programs. Studies such as this focusing on the experiences and knowledge of specific team members, such as the IT team, enhance tobacco-dependence treatment program implementation and can guide cancer centers and community oncology practices to implement these programs to improve patient outcomes.

Understanding how behaviour therapists use autism spectrum disorder diagnostic information for intervention planning.

Understanding how behaviour therapists incorporate diagnostic assessments into their intervention planning can help to streamline assessment procedures and facilitate communication. The objectives are to identify what information from the diagnostic assessment is received by behaviour therapists and which assessment elements are most important and relevant for treatment planning. Behaviour therapists, identified through Ontario registries, were surveyed about their use of diagnostic information in treatment planning. Seventy-one behaviour therapists completed the survey (response rate = 35.5%). The diagnostic information most frequently received by respondents included brief (69%) and detailed (49.2%) physician/psychologist report, speech/language assessment report (52.1%) and individualised education plan (50.7%). Most respondents indicated that information from the physician/psychologist report is often out-dated (74.6% Agree/Strongly Agree). There was variable agreement that the information in the diagnostic package influences the type and quantity of treatment. These findings demonstrate that while diagnostic assessments received by behaviour therapists are important to their planning, other independently obtained sources of information, such as client interviews, are relatively more important to this process. The diagnostic assessment is one tool to inform treatment planning; however, up-to-date information about the child's needs is likely to be more informative.

Prolonged nicotine exposure reduces aversion to the drug in mice by altering nicotinic transmission in the interpeduncular nucleus.

Nicotine intake is likely to result from a balance between the rewarding and aversive properties of the drug, yet the individual differences in neural activity that control aversion to nicotine and their adaptation during the addiction process remain largely unknown. Using a two-bottle choice experiment, we observed considerable heterogeneity in nicotine-drinking profiles in isogenic adult male mice, with about half of the mice persisting in nicotine consumption even at high concentrations, whereas the other half stopped consuming. We found that nicotine intake was negatively correlated with nicotine-evoked currents in the interpeduncular nucleus (IPN), and that prolonged exposure to nicotine, by weakening this response, decreased aversion to the drug, and hence boosted consumption. Lastly, using knock-out mice and local gene re-expression, we identified ß4-containing nicotinic acetylcholine receptors of IPN neurons as molecular and cellular correlates of nicotine aversion. Collectively, our results identify the IPN as a substrate for individual variabilities and adaptations in nicotine consumption.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. AIMS AND METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. CONCLUSIONS: The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Integrating Tobacco Treatment Into Oncology Care: Reach and Effectiveness of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers.

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness. METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified as currently smoking who received at least one evidence-based tobacco treatment component (eg, counseling and pharmacotherapy)-and smoking cessation effectiveness (effectiveness)-the proportion of patients reporting 7-day point prevalence abstinence at 6-month follow-up. Center-level differences in reach and effectiveness were examined by center characteristics, implementation strategies, and tobacco treatment components. RESULTS: Of the total 692,662 unique patients seen, 44,437 reported current smoking. Across centers, a median of 96% of patients were screened for tobacco use, median smoking prevalence was 7.4%, median reach was 15.4%, and median effectiveness was 18.4%. Center-level characteristics associated with higher reach included higher smoking prevalence, use of center-wide TTP, and lower patient-to-tobacco treatment specialist ratio. Higher effectiveness was observed at centers that served a larger overall population and population of patients who smoke, reported a higher smoking prevalence, and/or offered electronic health record referrals via a closed-loop system. CONCLUSION: Whole-center TTP implementation among inpatients and outpatients, and increasing staff-to-patient ratios may improve TTP reach. Designating personnel with tobacco treatment expertise and resources to increase tobacco treatment dose or intensity may improve smoking cessation effectiveness.

Operationalizing Leadership and Clinician Buy-In to Implement Evidence-Based Tobacco Treatment Programs in Routine Oncology Care: A Mixed-Method Study of the U.S. Cancer Center Cessation Initiative.

BACKGROUND: Delivering evidence-based tobacco dependence treatment in oncology settings improves smoking abstinence and cancer outcomes. Leadership engagement/buy-in is critical for implementation success, but few studies have defined buy-in or described how to secure buy-in for tobacco treatment programs (TTPs) in cancer care. This study examines buy-in during the establishment of tobacco treatment programs at National Cancer Institute (NCI)-designated cancer centers. METHODS: We utilized a sequential, explanatory mixed-methods approach to analyze quantitative data and qualitative interviews with program leads in the U.S.-based NCI Moonshot-supported Cancer Center Cessation Initiative (n = 20 Centers). We calculated descriptive statistics and applied structural coding and content analysis to qualitative data. RESULTS: At least 75% of participating centers secured health care system administrative, clinical, and IT leadership buy-in and support. Six themes emerged from interviews: engaging leadership, access to resources, leveraging federal funding support to build leadership interest, designating champions, identifying training needs, and ensuring staff roles and IT systems support workflows. CONCLUSIONS: Buy-in among staff and clinicians is defined by the belief that the TTP is necessary, valuable, and evidence based. Recognizing and securing these dimensions of buy-in can facilitate implementation success, leading to improved cancer outcomes.

Chronic nicotine increases midbrain dopamine neuron activity and biases individual strategies towards reduced exploration in mice.

Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making.

Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety.

Nicotine stimulates dopamine (DA) neurons of the ventral tegmental area (VTA) to establish and maintain reinforcement. Nicotine also induces anxiety through an as yet unknown circuitry. We found that nicotine injection drives opposite functional responses of two distinct populations of VTA DA neurons with anatomically segregated projections: it activates neurons that project to the nucleus accumbens (NAc), whereas it inhibits neurons that project to the amygdala nuclei (Amg). We further show that nicotine mediates anxiety-like behavior by acting on ß2-subunit-containing nicotinic acetylcholine receptors of the VTA. Finally, using optogenetics, we bidirectionally manipulate the VTA-NAc and VTA-Amg pathways to dissociate their contributions to anxiety-like behavior. We show that inhibition of VTA-Amg DA neurons mediates anxiety-like behavior, while their activation prevents the anxiogenic effects of nicotine. These distinct subpopulations of VTA DA neurons with opposite responses to nicotine may differentially drive the anxiogenic and the reinforcing effects of nicotine.

The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors.

The lack of intrinsic motivation to engage in, and adhere to, physical exercise has major health consequences. However, the neurobiological bases of exercise motivation are still unknown. This study aimed at examining whether the endocannabinoid system (ECS) is involved in this process. To do so, we developed an operant conditioning paradigm wherein mice unlocked a running wheel with nose pokes. Using pharmacological tools and conditional mutants for cannabinoid type-1 (CB1) receptors, we provide evidence that CB1 receptors located on GABAergic neurons are both necessary and sufficient to positively control running motivation. Conversely, this receptor population proved dispensable for the modulation of running duration per rewarded sequence. Although the ECS mediated the motivation for another reward, namely palatable food, such a regulation was independent from CB1 receptors on GABAergic neurons. In addition, we report that the lack of CB1 receptors on GABAergic neurons decreases the preference for running over palatable food when mice were proposed an exclusive choice between the two rewards. Beyond providing a paradigm that enables motivation processes for exercise to be dissected either singly or in concurrence, this study is the first to our knowledge to identify a neurobiological mechanism that might contribute to sedentary behavior.

Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors.

Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in living mice. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through ß2-containing (ß2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.

Prescription Drug Misuse and Associated Risk Behaviors among Public High School Students in Oklahoma: Data from the 2013 Oklahoma Youth Risk Behavior Survey.

PURPOSE: The purpose of this study was to assess the magnitude of prescription drug misuse among Oklahoma high school students, examine associated risk factors, and inform state-based prevention strategies. METHODS: Data from the 2013 Oklahoma Youth Risk Behavior Survey were used for this analysis and were representative of public school students in grades 9 through 12 in Oklahoma. Variables were examined using percentages and 95% confidence intervals. The chi-square test was used to test for differences in proportions. Logistic regression was used to produce adjusted odds ratios as measures of association between selected independent variables and prescription drug misuse. RESULTS: Nearly one in five students had ever used a prescription drug without a doctor's prescription. While there was no statistically significant difference of prescription drug misuse by gender or grade in the bivariate analysis, after covariate adjustment, females were 1.5 times more likely than males to have misused prescription drugs and twelfth graders were 1.7 times more likely than ninth graders to have misused prescription drugs. CONCLUSION: Students who had ever taken prescription drugs without a doctor's prescription were significantly more likely than students who had never taken prescription drugs without a doctor's prescription to have engaged in current tobacco use, current binge drinking, current marijuana use, and lifetime drug use and have a higher prevalence of suicide risk.

A Review of Barriers to Minorities' Participation in Cancer Clinical Trials: Implications for Future Cancer Research.

To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.

Fetal serum α-1 microglobulin for renal function assessment: comparison with ß2-microglobulin and cystatin C.

OBJECTIVE: To compare the prognostic value of fetal serum α1-microglobulin with that of ß2-microglobulin and cystatin C for postnatal renal function. METHOD: Retrospective study of α1-microglobulin, ß2-microglobulin, and cystatin C in fetal serum from 126 fetuses with congenital abnormalities of the kidney and urinary tract (73 and 53, respectively). Two groups were defined: group with normal renal function and group with renal failure. For live born infants, renal function was assessed on the basis of serum creatinine (cutoff 50 µmol/L) or glomerular filtration rate (cutoff 75 mL/min/1.73 m2) or both. In case of infant or fetal death, histological kidney lesions were considered. RESULTS: Significant differences (p < 0.001) were observed for the three markers between fetuses with good renal prognosis and those with renal failure (34.4 mg/L vs 67.6 mg/L for α1-microglobulin, respectively; 3.9 mg/L vs 7.35 mg/L, for ß2-microglobulin, respectively; and 1.67 mg/L vs 2.12 mg/L for cystatin C, respectively). Areas under receiver operator curves were used to compare the three markers, 0.96, 0.90, and 0.74 for ß2-microglobulin, α1-microglobulin, and cystatin C, respectively. CONCLUSION: Although α1-microglobulin is significantly different in fetuses with good renal prognosis and those with renal failure, overall, it is a less reliable prognostic marker than fetal serum ß2-microglobulin.

Down syndrome maternal serum marker screening after 18 weeks of gestation: a countrywide study.

OBJECTIVE: The objective of the study was to evaluate the efficacy of maternal serum markers in detecting Down syndrome after 18 weeks of gestation in women who book late for maternity care in a large national retrospective study. STUDY DESIGN: During the period 2007-2012, 27,648 women, regardless of maternal age (17.4% were 35 years old and over), were included in a late Down syndrome screening program (18(+0) to 35(+6) weeks) using the maternal serum markers alpha-fetoprotein and human chorionic gonadotrophin-beta. Samples were assayed in a single laboratory. A dataset of median markers previously established in our laboratory was used for risk calculation. The control group consisted of 27,648 women (14(+0) to 17(+6) weeks) randomly selected from the routine database. RESULTS: When the later screening group was compared with the standard second-trimester control group, the median multiples of medians (1.01 vs 0.98 for alpha-fetoprotein, 1.03 vs 0.98 for human chorionic gonadotrophin-beta), median risks (1 of 2414 vs 1 of 2720), false-positive rates (11.1% vs 11.6%), and trisomy 21 detection rates (83.3% vs 85.7%) did not differ significantly. CONCLUSION: Late Down syndrome maternal serum screening is feasible with a good sensitivity/specificity compromise throughout gestation and is of clinical value in late-booking women.

A review of the cluster survey sampling method in humanitarian emergencies.

Obtaining quality data in a timely manner from humanitarian emergencies is inherently difficult. Conditions of war, famine, population displacement, and other humanitarian disasters, cause limitations in the ability to widely survey. These limitations hold the potential to introduce fatal biases into study results. The cluster sample method is the most frequently used technique to draw a representative sample in these types of scenarios. A recent study utilizing the cluster sample method to estimate the number of excess deaths due to the invasion of Iraq has generated much controversy and confusion about this sampling technique. Although subject to certain intrinsic limitations, cluster sampling allows researchers to utilize statistical methods to draw inferences regarding entire populations when data gathering would otherwise be impossible.

The human papillomavirus vaccine in Canada.

Clinical studies have shown the human papillomavirus (HPV) vaccines to be very effective at preventing persistent infection by vaccine serotypes. The development of these new vaccines heralds a new era in cancer prevention. Gardasil, Merck's quadravalent HPV vaccine, has recently been licensed in Canada for women aged 9 to 26 years of age. It necessitates that health professionals become familiar with the vaccine, the evidence supporting its effectiveness and issues related to vaccine strategy, cost effectiveness, and remaining research questions. The vaccine is recommended in Canada for females aged 9 to 13 years and should also be offered to females aged 14 to 26 years. Ongoing research will determine the duration of protection conferred by the vaccine, and the potential need for booster doses. In conjunction with continued screening programs, the HPV vaccine offers the potential to dramatically reduce the burden of cervical cancer in Canada, and to do so in a cost-effective manner.